Clinical evaluation, research, and treatment of patients with manic-depressive illness, schizoaffective disorders, and anxiety disorders are the primary goals of the Section. Double-blind, placebo-controlled clinical trials are employed to evaluate routinely used and novel agents for the treatment of these disorders. A number of anticonvulsants are being employed, one of which - carbamazepine - has been demonstrated by our group to be clinically effective in the acute and prophylactic treatment of manic-depressive illness. We are seeking to identify clinical and biochemical markers of response to carbamazepine and other agents, and to elucidate the mechanisms of action of these drugs. Recent data suggest that noradrenergic and "peripheral-type" benzodiazepine mechanisms may be important to the anticonvulsant effects of carbamazepine; they may also be important to its psychotropic properties. However, like lithium carbonate, carbamazepine has a multitude of effects on a variety of neurotransmitter, modulator, and peptide substances, many of which may account for positive effects on mood and behavior. The Section also seeks to identify its regional alterations in brain electrophysiological and metabolic activity and relate these changes to behavioral and cognitive changes in affective illness. A clinical probe of limbic system excitability utilizing a novel provocative agent, procaine, is also being employed. Preliminary data suggest that this drug selectively increases fast activity over the temporal lobe in association with a variety of behavioral and cognitive alterations and secretion of cortisol, ACTH, and prolactin. Animal models of electrophysiological kindling, stimulant-induced behavioral sensitization, and unavoidable stress or "learned helplessness" are studied by the Section. The behavioral relevance of these models to clinical disorders is also explored, as well as possible basic neurophysiological and biochemical mechanisms which might underlie these long-term changes in behavior.